title: Metal ligand-binding specificities of the tyrosinase-related proteins.
abstract: The production of pigment in mammalian melanocytes requires the interaction of at least 3 melanogenic enzymes, which regulate the type and amount of melanins produced. All 3 known enzymes belong to the TRP gene family and share many common structural features, including two metal binding domains thought to be important to their catalytic functions. This study used radiolabeled metal ligand binding with autoradiography as well as reconstitution protocols to analyze the binding of metal cations to these enzymes. The results demonstrate that all 3 enzymes are capable of binding divalent metal cations; copper is bound to tyrosinase but not to TRP1 or TRP2. TRP2 requires zinc as its metal ligand, and small amounts of iron bound to TRP2; TRP1 did not bind copper, zinc or iron. Clearly, the specific binding of different metals by the TRPs is responsible for their distinct catalytic functions in melanogenesis.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Furumura
authors.forename: F
authors.initials: F
authors.lastname: Solano
authors.forename: N
authors.initials: N
authors.lastname: Matsunaga
authors.forename: C
authors.initials: C
authors.lastname: Sakai
authors.forename: R A
authors.initials: RA
authors.lastname: Spritz
authors.forename: V J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001051:Apoenzymes / Q000378:metabolism; D001345:Autoradiography; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000201:enzymology*; D008562:Membrane Glycoproteins; D019216:Metals, Heavy / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D001051:Apoenzymes; D008543:Melanins; D008562:Membrane Glycoproteins; D019216:Metals, Heavy; D011506:Proteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase